Whole-body positron emission tomography (PET) imaging with (18)F deoxyglucose (FDG) is a molecular imaging modality that detects metabolic alterations in tumor cells that are common to neoplastic cells. FDG-PET has recently been approved by the Health Care Finance Administration for Medicare reimbursement for diagnosing, staging, and restaging lung cancer, colorectal cancer, lymphoma, melanoma, head and neck cancer, and esophageal cancer. This review discusses the scientific evidence that led to the emergence of PET imaging as an accepted clinical tool in patients with solitary pulmonary nodules, lung cancer, colorectal cancer, melanoma, lymphoma, breast cancer, and other cancers. When possible, we compare the performance of PET to that of anatomical imaging. We discuss future clinical applications of this imaging modality.